Compared with the control group, the expression of GRP78 and PERK signaling protein (PERK, eIF2α, and CHOP) in the GanDouLing-Penicillium group was markedly up-regulated, and apoptosis indicators (caspase-3 and caspase-12) were obviously increased, TUNEL assay showed significant increase in apoptosis of cerebrovascular endothelial cells, which suggested that GanDouLing-Penicillium improves cerebrovascular injury through PERK/eIF2α/CHOP ER stress pathway in the WD mouse model. This evidence concerns the gene EIF2AK3 and Wilson disease.